Solid–liquid multiphase mixing is of fundamental importance for the pharmaceutical industry since the achievement of the appropriate solid dispersion level influences both the synthesis of the active pharmaceutical ingredients and the manufacturing process of final dosage forms. The achievement of a spatially and temporally uniform dispersion of the active agent is a frequent goal of many pharmaceutical operations involving dispersed solids in liquids.

In this work the manufacturing process required to fabricate a film strip incorporating particles of an active material has been analyzed. This involves, at first, the preparation of a dispersion of the drug particles in an aqueous medium and, secondly, the homogenization of the latter with a gelling agent to obtain a suspension of the active.In addition, the film strip manufacturing process necessitates the drug particles to have an appropriate size compatible with the film thickness. The particle size distribution needs also to be narrow. Therefore a key aspect that has been addressed is the particle de-agglomeration process. The operating conditions that generate the necessary particle size distribution have been studied.

Vessels of different volumes were considered: 20, 11 and 5 L. All the tanks were baffled, cylindrical and flat bottomed. The same geometrical proportions have been used for the different tanks examined: the baffle width-to-tank diameter ratio of 0.1 and the ratio of liquid height, H, to tank diameter, T, of 1 (H=T). The system was provided with a centrally mounted pitched-blade turbine (PBT) used to suspend the solids, and a high speed homogenizer that breaks up the agglomerates formed by primary particles.

A water-solid system was considered at first in order to characterize its behavior for different agitation speeds and solid concentrations. Solids of the same size and density as the typical active ingredients to be eventually used in the film strips were used as the dispersed phase. For the first experiments, surrogate silica particles with primary particle size of 16 nm and initial agglomerate size of ~30 microns were selected.

The effect of high-shear agitation on particle de-agglomeration and the hydrodynamic forces generated in the solid-liquid system have been characterized in terms of: final agglomerates size, time to reach the asymptotic value of the mean agglomerate size, and quality of the particle size distribution.

The results show that the disruptive forces generated by the homogenizer are strong enough to break up the agglomerates and to reduce their size to the submicron range. Moreover, the ratio between the total tank volume and the volume effectively affected by the homogenizer's action influences the time needed by the system to reach an asymptotic value for the mean agglomerates diameter.